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Identification of T-cell epitopes derived from HBSP protein of HBV

Inventors: Marie-Louise MICHEL et al.

Description of invention: 

HBSP protein (hepatitis B spliced protein) has been detected in liver biopsy specimens from patients with chronic active hepatitis. Antibodies directed against this protein have been found in more than 1/3 of sera from chronic HBV carriers. More recently, it was demonstrated that HBSP protein expression was correlated with the viral replication and the onset of hepatic fibrosis. This suggests a direct involvement of HBSP protein in the pathogenesis of liver disease. However, HBSP-specific T-cell response has not been studied yet. To characterize immune responses specific for the HBSP protein and define peptide sequences recognized by T cells, we immunized mice transgenic for human MHC I molecules (HLA-A2, HLA-B7) with DNA vectors encoding the HBSP protein. Thus we identified 3 HBSP peptides recognized by T cells in the context of HLA-A2 molecules and two HLA-B7 restricted epitopes among which one is immunodominant. Importantly, a set of overlapping peptides covering the HBSP sequence induced significant HBSP-specific T cell responses in peripheral blood mononuclear cells from patients with chronic hepatitis. The response was multispecific as several peptides were recognized by CD4+ and CD8+ human T cells.
This study will help at defining HBSP-specific T cell responses in HBV infected patients in different clinical settings. A correlation between T-cell responses and the onset of fibrosis will be searched.

 Potential applications:

 Identification of epitopic sequences derived from HBSP protein will have important diagnostic and therapeutic issue for the treatment of chronic hepatitis B.

Patent Status:
 

 French patent application filed on June 29th, 2005 under the number FR 05 06672 and published under the number 2887884
 International patent application filed on June 29th, 2006 under the number PCTFR 06001532 and published under the number WO2007003775

 Publications:

 Hepatitis B virus splice-generated protein induces T-cell responses in HLA-transgenic mice
and HBV-infected patients.
M. Mancini-Bourgine, F. Bayard, P. Soussan, Q. Deng, Y.-C. Lone, D. Kremsdorf, M-L Michel
Journal of Virology, May 14 2007 vol 81, issue 10.


 

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